METABOLIC SYNDROME AND RELATED DISORDERS Volume 5, Number 4, 2007 © Mary Ann Liebert, Inc. Pp. 315–322 DOI: 10.1089/met.2007.0007 Docosahexaenoic Acid (DHA) But Not Eicosapentaenoic Acid (EPA) Prevents Trans-10, Cis-12 Conjugated Linoleic Acid (CLA)–Induced Insulin Resistance in Mice MADHURI VEMURI, 1 DARSHAN S. KELLEY, 1 BRUCE. E. MACKEY, 2 REUVEN RASOOLY, 1 GIOVANNI BARTOLINI 1 ABSTRACT Background: The objective of this study was to investigate if eicosapentaenoic acid (20:5n-3, EPA) or docosahexaenoic acid (22:6n-3, DHA) or both would prevent conjugated linoleic acid (CLA)–induced insulin resistance and fatty liver. Methods: Eight-week-old, pathogen-free C57BL/6N female mice (10 per group) were fed ei- ther a control diet or diets containing t10, c12-CLA (0.5 wt %), CLA + DHA (0.5% + 1.5 wt %), or CLA + EPA (0.5% + 1.5 wt %) for 8 weeks prior to sacrifice and tissue collection. Results: CLA supplementation caused an 8.9-fold increase in circulating insulin, a 2.6-fold increase in liver weight, and a 6.2-fold increase in the weight of total lipids in the liver as compared with the corresponding values in the control group. DHA prevented the CLA-in- duced insulin resistance, while EPA was ineffective. Both EPA and DHA prevented CLA-in- duced fatty liver and reduced weights of total liver lipids to the levels of the control group. CLA also reduced the plasma leptin and adiponectin concentrations to approximately 15% of those in the control group. Both EPA and DHA partially restored the CLA-induced decrease in leptin, but only DHA partially restored the plasma adiponectin. Conclusions: Our results suggest that DHA but not EPA in fish oils may reduce insulin re- sistance which may be mediated through an increase in circulating adiponectin. These find- ings may have clinical implications in the dietary management of patients at risk of insulin resistance and diabetes. 315 INTRODUCTION C ONJUGATED LINOLEIC ACID (CLA) refers to linoleic acid isomers having conjugated double bonds. The two isomers that have been most commonly studied are c9, t11-CLA and t10, c12-CLA. Dairy products and ruminant meats are the major sources of c9, t11-CLA, while t10, c12-CLA is found primarily in par- tially hydrogenated vegetable oils. 1 Supple- menting human as well as animal diets with CLA has been claimed to decrease body fat and also reduce the incidences of diabetes, atherosclerosis and cancer, 2–4 and references 1 Western Human Nutrition Research Center, ARS, USDA, and Department of Nutrition, University of California, Davis, California 2 Western Regional Research Center, ARS, USDA, Albany, CA. Reference to a company or product name does not imply approval or recommendation of the product by the US Department of Agriculture to the exclusion of others that may be suitable